Chromosome imbalances in syndromic hearing loss

Abstract

The cause of hearing impairment has not been elucidated in a large proportion of patients. We screened by 1-Mb array-based comparative genomic hybridization (aCGH) 29 individuals with syndromic hearing impairment whose clinical features were not typical of known disorders. Rare chromosomal copy number changes were detected in eight patients, four de novo imbalances and four inherited from a normal parent. The de novo alterations define candidate chromosome segments likely to harbor dosage-sensitive genes related to hearing impairment, namely 1q23.3-q25.2, 2q22q23, 6p25.3 and 11q13.2-q13.4. The rare imbalances also present in normal parents might be casually associated with hearing impairment, but its role as a predisposition gene remains a possibility. Our results show that syndromic deafness is frequently associated with chromosome microimbalances (14-27%), and the use of aCGH for defining disease etiology is recommended.

Genomic copy number alterations in non‐syndromic hearing loss

“…An earlier study from our group in patients with syndromic hearing loss revealed that chromosomal imbalances are a common cause of the phenotypes . In recent years, some publications have reported that rare copy number alterations are also a cause of non‐syndromic hearing loss .…”

“…To date, 87 genes for NSHL have been identified (http://hereditaryhearingloss.org/). A previous study by our group showed that syndromic deafness is frequently associated with chromosome micro‐imbalances , while chromosomal alterations in non‐syndromic patients tend to be both rare and small, pinpointing specific genes .…”

A novel KCNQ4 mutation and a private IMMP2L-DOCK4 duplication segregating with nonsyndromic hearing loss in a Brazilian family

“…Some mutation mechanisms, such as deletions and duplications, have been under-studied, and the contribution of DNA copy-number variations to hearing loss has only recently begun to be investigated. 2–4 …”

“…To evaluate the contribution of microdeletions and microduplications of genes that might have a role in the etiology of syndromic and nonsyndromic deafness, we selected 17 candidate genes among the genes involved in the rare microimbalances detected by Catelani et al 3 for investigation by multiplex ligation-dependent probe amplification (MLPA). Our investigated cohort comprised 132 probands from pedigrees presenting with syndromic or nonsyndromic deafness.…”

Proposta de genes relacionados à deficiência auditiva sindrômica baseada em Variações do Número de Cópias (CNVs) e Perda de Heterozigose (LOH)

“…Técnicas que permitem a detecção de CNVs têm sido amplamente utilizadas no estudo de casos sindrômicos (CALLIER, et al, 2008;NAGAMANI, et al, 2009;COSTAIN, et al, 2013). -SANTOS et al, 2006CATELANI et al, 2009. (AFZAL, et al, 2000;PERSON et al, 2010;GAO, et al, 2011;YANG, 2012;WHITE, et al, 2015 (MITCHEM et al, 2002;NAZ et al, 2002GLEASON et al, 2009.…”